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European Radiology

, Volume 22, Issue 4, pp 821–831 | Cite as

Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

  • M. J. Gollub
  • D. H. Gultekin
  • O. Akin
  • R. K. Do
  • J. L. FuquaIII
  • M. Gonen
  • D. Kuk
  • M. Weiser
  • L. Saltz
  • D. Schrag
  • K. Goodman
  • P. Paty
  • J. Guillem
  • G. M. Nash
  • L. Temple
  • J. Shia
  • L. H. Schwartz
Gastrointestinal

Abstract

Objective

To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer.

Methods

In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, Ktrans, kep, ve, AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman’s Rank correlation was used. For categorical variable comparison, the Kruskal–Wallis test was used. P ≤ 0.05 was considered significant.

Results

Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy Ktrans (mean 0.5 min−1 vs. 0.2 min−1, P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone.

Conclusion

After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR.

Key Points

  • Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours.

  • These objective quantitative measures may be more helpful than subjective imaging alone

  • Some parameters differed markedly between completely responding and incompletely responding rectal cancers.

  • Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.

Keywords

Rectal cancer DCE-MRI Neoadjuvant Chemotherapy Response 

Notes

Acknowledgements

We would like to thank Michael Sohn for his invaluable help with database management.

References

  1. 1.
    Hartley A, Ho KF, McConkey C et al (2005) Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol 78:934–938PubMedCrossRefGoogle Scholar
  2. 2.
    Kalff V, Ware R, Heriot A et al (2009) Radiation changes do not interfere with postchemoradiation restaging of patients with rectal cancer by FDG PET/CT before curative surgical therapy. Int J Radiat Oncol Biol Phys 74:60–6PubMedCrossRefGoogle Scholar
  3. 3.
    Kalff V, Duong C, Drummond EG et al (2006) Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provide prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. J Nucl Med 47:14–22PubMedGoogle Scholar
  4. 4.
    Suppiah A, Hunter IA, Cowley J et al (2009) Magnetic resonance imaging accuracy in assessing tumor down-staging following chemoradiation in rectal cancer. Colorectal Dis 3:249–53CrossRefGoogle Scholar
  5. 5.
    Goh V, Padhani AR, Rasheed S (2007) Functional imaging of colorectal cancer angiogenesis. Lancet Oncol 8:245–55PubMedCrossRefGoogle Scholar
  6. 6.
    Kierkels RG, Backes WH, Janssen MHM et al (2010) Comparison between perfusion computed tomography and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer. Int J Radiation Oncology Biol Phys 77:400–408CrossRefGoogle Scholar
  7. 7.
    De Lussanet QG, Backes WH, Griffen AW et al (2005) Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer. Int J Radiat Oncol Biol Phys 13:1309–1315CrossRefGoogle Scholar
  8. 8.
    Atkin G, Taylor NJ, Daley FM et al (2006) Dynamic contrast-enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis. Br J Surg 93:992–1000PubMedCrossRefGoogle Scholar
  9. 9.
    Kremser C, Trieb T, Rudisch A et al (2007) Dynamic T1 mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. J Magn Reson Imaging 26:662–671PubMedCrossRefGoogle Scholar
  10. 10.
    Sahani DV, Kalva SP, Hamberg LM et al (2005) Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: initial observations. Radiology 234:785–792PubMedCrossRefGoogle Scholar
  11. 11.
    Dinter DJ, Horisberger K, Zechmann C et al (2009) Can dynamic MR imaging predict response in patients with rectal cancer undergoing Cetuximab-based neoadjuvant chemoradiation? Onkologie 32:86–93PubMedCrossRefGoogle Scholar
  12. 12.
    De Vries A, Griebel J, Kremser C et al (2000) Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implications for therapy. Radiology 217:385–391PubMedGoogle Scholar
  13. 13.
    DeVries AF, Griebel J, Kremser C et al (2001) Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma. Cancer Res 61:2513–2516PubMedGoogle Scholar
  14. 14.
    Habr-Gama A, Perez RO, Wynn G et al (2010) Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 53:1692–1698PubMedCrossRefGoogle Scholar
  15. 15.
    Capirci C, Valentini V, Cionini L et al (2008) Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 72:99–107PubMedCrossRefGoogle Scholar
  16. 16.
    Rödel C, Martus P, Papadoupolos T et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–96PubMedCrossRefGoogle Scholar
  17. 17.
    Kety SS (1951) The theory and applications of the exchange of inert gas at the lungs and tissues. Pharmacol Rev 3:1–41PubMedGoogle Scholar
  18. 18.
    Weinmann HJ, Laniado M, Mützel W (1984) Pharmacokinetics of Gd DTPA/dimeglumine after intravenous injection into healthy volunteers. Physiol Chem Phys Med NMR 16:167–172PubMedGoogle Scholar
  19. 19.
    Tofts PS, Kermode AG (1991) Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17:357–67PubMedCrossRefGoogle Scholar
  20. 20.
    Jarnagin WR, Schwartz LH, Gultekin DH et al (2009) Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol 20:1589–95PubMedCrossRefGoogle Scholar
  21. 21.
    Lockhart AC, Rothenberg ML, Dupont J et al (2010) Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 28:207–14PubMedCrossRefGoogle Scholar
  22. 22.
    Shia J, Guillem JG, Moore HG et al (2004) Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol 28:215–223PubMedCrossRefGoogle Scholar
  23. 23.
    Bewick V, Cheek L, Ball J (2004) Statistics review 10: further nonparametric methods. Crit Care 8:196–199PubMedCrossRefGoogle Scholar
  24. 24.
    Kim YH, Kim DY, Kim TH et al (2005) Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer. Int J Radiat Oncol Biol Phys 62:761–768PubMedCrossRefGoogle Scholar
  25. 25.
    Padhani AR, Dzik-Jurasz A (2004) Perfusion MR imaging of extracranial tumor angiogenesis. Top Magn Reson Imaging 15:41–57PubMedCrossRefGoogle Scholar
  26. 26.
    Willett CG et al (2004) Direct evidence that VEG specific antibody Bevacizumab has anti-vascular effects in human vascular cancer. Nat Med 10:145–147PubMedCrossRefGoogle Scholar
  27. 27.
    Tofts PS, Phil D, Brix G et al (1999) Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10:223–232PubMedCrossRefGoogle Scholar
  28. 28.
    Lankester KJ, Taylor NJ, Stirling JJ et al (2007) Dynamic MRI for imaging tumor microvasculature: comparison of susceptibility and relaxivity techniques in pelvic tumors. J Mag Reson Imaging 25:796–805CrossRefGoogle Scholar
  29. 29.
    George ML, Dzik-Jurasz ASK, Padhani AR et al (2001) Non-invasive methods of assessing angiogenesis and their value in predicting response to treatment in colorectal cancer. Br J Surg 88:1628–1636PubMedCrossRefGoogle Scholar
  30. 30.
    Brown JM, Giacca AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416PubMedGoogle Scholar
  31. 31.
    Quah HM, Chou JF, Gonen M et al (2008) Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer 113:57–64PubMedCrossRefGoogle Scholar
  32. 32.
    Habr-Gama A, Perez RO, Nadalin W et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240:711–718PubMedGoogle Scholar

Copyright information

© European Society of Radiology 2011

Authors and Affiliations

  • M. J. Gollub
    • 1
  • D. H. Gultekin
    • 1
  • O. Akin
    • 1
  • R. K. Do
    • 1
  • J. L. FuquaIII
    • 1
  • M. Gonen
    • 2
  • D. Kuk
    • 2
  • M. Weiser
    • 3
  • L. Saltz
    • 4
  • D. Schrag
    • 5
  • K. Goodman
    • 6
  • P. Paty
    • 3
  • J. Guillem
    • 3
  • G. M. Nash
    • 3
  • L. Temple
    • 3
  • J. Shia
    • 7
  • L. H. Schwartz
    • 8
  1. 1.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Dana Farber Cancer InstituteBostonUSA
  6. 6.Department of Radiation OncologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  7. 7.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  8. 8.Department of RadiologyColumbia University Medical Center/New York Presbyterian HospitalNew YorkUSA

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